Frederick J. De Serr, A. Hollaender

Chemical Mutagens (eBook, PDF)

Principles and Methods for Their Detection Volume 8

• Format: PDF

Produktbeschreibung

Volume 8 of Chemical Mutagens covers a wide range of topics in this continuously changing field. This volume includes chapters on the detection of genetic damage in mammalian sperm both at specific loci and over the entire genome. The discussion of in vitro techniques for working with mammalian cells covers not only specific locus assays but also cellular activation systems. Another chapter extensively discusses the need for a revised protocol for the micronucleus assay. Structure activity relationships are investigated in a chapter dealing with hair dye constituents. One of the most comprehensive chapters deals with problems associated with the detection of mutagenic effects in defined human populations. Finally, there is a detailed presentation of a comprehensive study tabulating the genetic bioassay data on some known or suspected human carcinogens. In keeping with our policy of publishing important legislation in the area of chemical mutagens, we have also included the Council of the European Communities Directive of 18 September 1979. Frederick J. de Serres Research Triangle Park, North Carolina vii Contents Chapter 1 Detection of Effects of Mutagens in Human Populations George R. Hoffmann 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Monitoring Progeny for Evidence of Germ-Cell Mutations. . . . . 3 2. 1. The Classical Approach: Phenotypic Monitoring . . . . . . . 3 2. 2. Monitoring for Changes in Gene Products . . . . . . . . . . . 7 3. Detection of Gene Mutations in Somatic Cells. . . . . . . . . . . . . 9 3. 1. Drug-Resistant Lymphocytes . . . . . . . . . . . . . . . . . . . . . . 9 3. 2. Hemoglobin Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4. Nongenetic Indicators of Mutagen Exposure . . . . . . . . . . . . . 21 4. 1. Alkylation of Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4. 2. DNA Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

---

Dieser Download kann aus rechtlichen Gründen nur mit Rechnungsadresse in A, B, BG, CY, CZ, D, DK, EW, E, FIN, F, GR, HR, H, IRL, I, LT, L, LR, M, NL, PL, P, R, S, SLO, SK ausgeliefert werden.

Produktdetails

• Verlag: Springer New York
• Seitenzahl: 386
• Erscheinungstermin: 6. Dezember 2012
• Englisch
• ISBN-13: 9781461336945
• Artikelnr.: 44176552

Inhaltsangabe

1 Detection of Effects of Mutagens in Human Populations.- 1. Introduction.- 2. Monitoring Progeny for Evidence of Germ-Cell Mutations.- 2.1. The Classical Approach: Phenotypic Monitoring.- 2.2. Monitoring for Changes in Gene Products.- 3. Detection of Gene Mutations in Somatic Cells.- 3.1. Drug-Resistant Lymphocytes.- 3.2. Hemoglobin Variants.- 4. Nongenetic Indicators of Mutagen Exposure.- 4.1. Alkylation of Proteins.- 4.2. DNA Damage.- 5. Testing for Mutagenic Substances in Body Fluids.- 6. Detection of Altered Sperm.- 6.1. Morphological Sperm Abnormalities.- 6.2. Double Y Bodies in Sperm.- 6.3. Gene Mutations in Sperm.- 7. Summary.- 8. References.- 2 The Use of Intact Cellular Activation Systems in Genetic Toxicology Assays.- 1. Introduction.- 2. Mammalian Cell Mutagenesis.- 2.1. Fibroblast-Mediated Mutagenesis.- 2.2. Hepatocyte-Mediated Mutagenesis.- 2.3. Target Organ and Cell Type Specificities.- 2.4. Studies Using Human Cells.- 3. Bacterial Mutagenesis.- 4. Sister Chromatid Exchange and Chromosome Aberrations.- 5. Cell-Mediated Transformation.- 6. Cytotoxicity and Nucleic Acid Interactions.- 7. Discussion.- 8. Summary.- 9. References.- 3 The Mouse Spot Test As a Predictor of Heritable Genetic Damage and Other Endpoints.- 1. Introduction.- 2. Relation to Measures of Heritable Mutations.- 2.1. Genetic Comparisons.- 2.2. Calculation of
Unit
Mutation Rates.- 2.3. Quantitative Comparisons of SLT and MST Results.- 3. Relation to Other Endpoints.- 4. Summary.- 5. References.- 4 The Bone Marrow Micronucleus Assay: Rationale for a Revised Protocol.- 1. Introduction.- 2. Kinetics of Erythropoiesis.- 3. Rationale for the Basic Aspects of the Protocol.- 3.1. Treatment Regimen.- 3.2. Sample Intervals.- 4. Protocol.- 4.1. General Approach.- 4.2. Protocol Specifics.- 4.3. Spindle Poisons.- 5. Statistical Analysis.- 6. Conclusions.- 7. References.- 5 Relationships between the Chemical Structure and Mutagenic Activity of Monocyclic Aromatic Amines.- 1. Introduction.- 2. Bacterial Strains.- 3. Experimental Methods.- 4. Chemicals.- 5. Mutagenicity Data and Their Interpretation.- 5.1. The 2,4-Diaminoalkoxybenzenes.- 5.2. m-Diaminobenzene and Its 2,4-Diaminoalkylbenzene Derivatives.- 5.3. Nitro-p-phenylenediamine Derivatives.- 5.4. The 3-Amino-4-nitrophenols and the 4-Amino-3- nitrophenols.- 6. Possible Pitfalls in Studies of Structure-Activity Relationships.- 7. Conclusions.- 8. References.- 6 The Measurement of Recessive Lethal Mutations in the Mouse.- 1. Introduction.- 2. Haldane
s Method of Detecting Lethals.- 3. The Backcross Method of Detecting Lethals.- 3.1. Choice of Animals for Studies.- 3.2. Treatment and Breeding Schedule.- 3.3. Identification of Translocation Bearers.- 3.4. The Backcross Matings.- 3.5. Controls.- 4. Irradiation Treatment of Male Germ Cells.- 5. Irradiation Treatment of Female Germ Cells.- 6. Chemical Mutagen Induction of Recessive Lethal Mutations.- 7. Dominant Effects of Recessive Lethal Mutations.- 8. Conclusions.- 9. References.- 7 Chemically Induced Changes in Sperm in Animals and Humans.- 1. Introduction.- 2. The F0 Mouse Sperm Head Morphology Assay.- 2.1. Reproducibility between Laboratories.- 2.2. Results.- 2.3. Method Development.- 3. The F1 Sperm Head Morphology Assay.- 3.1. Genetic Basis of F1 Mouse Sperm Head Morphology Assay.- 3.2. Results.- 3.3. The Potential of the F1 Assay.- 4. Induced Sperm Abnormalities in Humans.- 4.1. Assays Used in the Evaluation of Human Sperm.- 4.2. Comparison of Human and Animal Semen Quality.- 4.3. The Uses of Semen Analysis in Humans.- 5. Implications of Alterations in Human Sperm Quality.- 5.1. Reproductive Implications.- 5.2. Mutagenic Implications.- 5.3. Carcinogenicity Implications.- 6. The Advantages of Sperm Assays.- 7. Recommendations for Future Research and Development.- 8. References.- 8 Mutational Analysis in Cultured Human-Hamster Hybrid Cells.- 1. Introduction.- 2. Origin of Specific Lethal Antisera and Human-Hamster Hybrid Cells.- 2.1. Demonstration of Antisera Specificity.- 2.2. Preparation of Human
Hamster Hybrid Cells Containing Specific Human Chromosomes.- 3. Characterization of the AL Hybrid.- 3.1. Origin of the AL Hybrid.- 3.2. Assignment of the AL Surface Antigens to Human Chromosome 11.- 3.3. Analysis of the AL Antigenic System: Demonstration That the AL Antigenic System Is Composed of a Subset of Activities a1, a2, and a3.- 3.4. Regional Gene Mapping of Markers on Human Chromosome 11.- 3.5. Complementation Analysis of the AL Markers.- 3.6. Biochemical Characterization of the a1 Surface Antigen.- 4. Mutation Studies.- 4.1. Source of Antisera and Complement.- 4.2. Treatment of AL Cells with Suspected Mutagens.- 4.3. Scoring Loss of the a1+ Surface Marker.- 4.4. Yield of a1? Mutants.- 4.5. Fluctuation Analysis for Spontaneous Loss of a1+.- 4.6. Analysis of Induced Loss of Other Markers from Chromosome 11.- 4.7. Production of Mutations by Colcemid.- 5. Conclusions.- 6. References.- 9 Genetic Toxicology of Some Known or Suspected Human Carcinogens.- 1. Introduction.- 2. Chemical Selection.- 3. Method of Literature Review.- 4. Results.- 5. Discussion.- 5.1. Human Respiratory Tract Carcinogens.- 5.2. Human Hematolymphopoietic System Carcinogens.- 5.3. Human Bladder Carcinogens.- 5.4. Human Liver Carcinogens.- 5.5. Other Human Carcinogens or Suspected Human Carcinogens.- 6. Summary and Conclusions.- 7. Appendix: Complete Data Base.- 8. References.- 10 Control of Commercial Chemicals: The Sixth Amendment to the Directive on Dangerous Chemical Substances (79/83 I/EEC) Adopted by the Council of the European Communities.- 1. Introduction.- 2. Text of the Sixth Amendment to the Directive on Dangerous Chemical Substances Adopted by the Council of the European Communities.- 3. References.

---

1 Chemical Mutagens and Sister-Chromatid Exchange.- 1. Introduction.- 1.1. Advantages of Studying Sister-Chromatid Exchange.- 1.2. Development of Modern Techniques.- 2. Sister-Chromatid Exchange as a Measure of Chromosome Damage.- 2.1. Variation in the Baseline Frequency of Sister-Chromatid Exchange.- 2.2. Induction of Sister-Chromatid Exchanges by Ultraviolet Light, X Rays, and Viruses.- 2.3. What Are Sister-Chromatid Exchanges?.- 2.4. Factors That Affect the Frequency of Sister-Chromatid Exchanges Induced by Chemicals.- 3. Systems and Methods t2.- 4. Summary.- 5. References.- 2 Modification of Mutagenic Activity.- 1. Introduction. 41 2. Factors That Influence Metabolic Activation t2.- 3The Detection of Chemical Mutagens/Carcinogens by DNA Repair and Mutagenesis in Liver Cultures.- 1. Introduction.- 2. Types of Chemical Carcinogens.- 3. Metabolic Activation Capability of Liver.- 4. Liver Cultures.- 4.1. Hepatocyte Primary Cultures.- 4.2. Long-Term Epithelial Cultures.- 5. Carcinogen Metabolism in Liver Cultures.- 6. Hepatocyte Primary Culture/DNA Repair Assay.- 6.1. Autoradiographic Assay.- 6.2. Liquid Scintillation Counting Assay.- 7. Mutagenesis of Rat Liver Epithelial Lines.- 8. Hepatocyte-Mediated Mutagenesis of Rat Liver Epithelial Lines.- 9. Discussion.- 10. References.- 4 Commercial Screening of Environmental Chemicals.- 1. Introduction.- 2. Transfer of Technology.- 3. Goals of Genetic Toxicology in Chemical Safety Evaluation.- 3.1. Approaches for Assay System Deployment in the Identification of Genotoxic Substances.- 3.2. Application of Test Results to Health and Safety Considerations.- 3.3. Application of Test Results to Management Decisions Concerning Chemical Development.- 4. Technical Operation Requirements.- 4.1. Facilities.- 4.2. Data Management and Control.- 4.3. Chemical Storage and Waste Disposal.- 5. Legal Operation Requirements.- 5.1. Laboratory Safety and Employee Monitoring.- 5.2. Good Laboratory Practices and Guidelines.- 6. Summary.- 7. References.- 5 Determining the DNA-Modifying Activity of Chemicals Using DNA-Polymerase-Deficient Escherichia coli.- 1. Introduction.- 2. Materials and Methods.- 2.1. Media.- 2.2. Preservation of Tester Strains.- 3. Standard Assay.- 3.1. Preparation of Cultures for Testing.- 3.2. Important Precautions.- 3.3. Procedure for the Pol A Assay.- 3.4. Preparation of Test Agents.- 3.5. Standards.- 4. Modified Assay.- 4.1. Modification of the Pol A1-Assay (Liquid Suspension).- 4.2. Procedure.- 5. Microsomal Activation.- 5.1. Preparation of Rat Liver S-9 Fraction.- 5.2. Plate Assay.- 5.3. Liquid Assay Procedure.- 6. Results and Discussion.- 6.1. Standard Assay.- 6.2. Modified (Liquid) Assay.- 7. Comparison of the Pol A and Salmonella Assays.- 8. References.- 6 Screening of Environmental Chemical Mutagens by the Rec-Assay System with Bacillus subtilis.- 1. Introduction.- 2. Principles and Related Background of the Rec-Assay.- 3. Experimental Procedures.- 3.1. Rapid Streak Method (without Metabolic Activation).- 3.2. Quantitative Analysis by the Spore Rec-Assay (with and without Metabolic Activation).- 3.3. Quantitative Liquid Method (with and without Metabolic Activation).- 4. Examples of Detection of Chemical Mutagens by the Rec-Assay Procedures.- 4.1. Food Additives.- 4.2. Pesticides.- 4.3. Metals.- 4.4. Miscellaneous.- 5. Rec-Assays on Chemical Carcinogens.- 6. References.- 7 Transformation of Syrian Hamster Embryo Cells by Diverse Chemicals and Correlation with Their Reported Carcinogenic and Mutagenic Activities.- 1. Introduction.- 2. Mammalian Cell Transformation Systems as Prescreens for Identifying Carcinogens in the Environment.- 3. Hamster Embryo Cell in Vitro Carcinogenesis Bioassay.- 3.1. Standardization of the Bioassay Procedure by the Use of Cryopreserved Cells.- 3.2. Criteria for Positive Response.- 4. Correlation of Transformation Response with Reported Carcinogenicity and Mutagenicity.- 4.1. Direct-Acting Alkylating Agents.- 4.2. Polycyclic Aromatic Hydrocarbons.- 4.3. Nitrosamines and Nitrosamides.- 4.4. Aromatic Amines, Aminoazo Dyes, and Nitro Compounds.- 4.5. Carcinogenic Metallic Salts.- 4.6. Miscellaneous Compounds.- 5. Metabolic Activation.- 6. A Battery vs. a Tier of Short-Term Tests for Identifying Potentially Carcinogenic Chemicals.- 7. Conclusions.- 8. References.- 8 Chemical Mutagenesis in the Silkworm.- 1. Introduction.- 2. Methods for Mutation Detection in the Silkworm.- 2.1. Correlation between Developmental Stages of the Silkworm and the Stages of Spermatogenesis and Oogenesis.- 2.2. Specific Locus Method.- 2.3. Dominant Lethal Method.- 2.4. Detection of Nondisj unction and Polyploidy.- 3. Procedures for Administration of Chemicals.- 3.1. Oral Administration.- 3.2. Injection.- 3.3. Soaking of Eggs in Chemical Solution.- 3.4. Gas (Aerosol) Treatment.- 4. Sensitivity.- 4.1. Strain Difference.- 4.2. Variation with the Progress of Germ-Cell Development.- 5. Mosaics and Delayed Mutagenesis.- 5.1. Preponderance of Mosaics.- 5.2. Delayed Mutagenic Effect.- 6. Exploitation of a Sensitive Test System with Oocytes.- 6.1. Effective Stage of Injected Chemicals in the Oocyte System.- 7. Screening of Environmental Mutagenic Compounds.- 8. Modification of Mutagenicity by Metabolic Activation.- 9. Conclusion.- 10. References.- 9 The Use of Short-Term Tests in the Isolation and Identification of Chemical Mutagens in Complex Mixtures.- 1. Introduction.- 2. Extraction Methodology.- 2.1. Rapid, Simple Extraction Methods.- 2.2. Class Fractionation.- 3. Mutagenesis Assay Methodology.- 3.1. Microbial Mutagenesis Assays.- 3.2. Comparative Mutagenesis.- 3.3. Precautions for the Use of Short-Term Mutagenicity Assays.- 4. References.- 10 Mathematical Analysis of Mutation-Induction Kinetics.- 1. Introduction.- 2. Definitions.- 3. Stochastic Description of Mutagenesis and Killing.- 4. Formal Dose-Response Patterns.- 5. The Linear Response Pattern (Lk,Lm).- 6. Nonlinear Response Patterns.- 6.1. Initial Slope of Yield Curves.- 6.2. Positions of Yield Maxima.- 6.3. Magnitude of Yield Maxima.- 6.4. Lethal Hit Units for Nonlinear Cases.- 6.5. Integral Yields for Nonlinear Cases.- 7. Illustrative Calculations of Yield Curves.- 8. Relative Mutagenic Efficiency (RME).- 9. Stochastic Dependence of Mutation and Killing.- 10. Repair-Mediated Mutagenesis.- 11. Concluding Remarks.- 12. Summary.- 13. Appendix t2.- 11 Comparison of the Mutagenic Effect of Ultraviolet Radiation and Chemicals in Normal and DNA-RepairDeficient Human Cells in Culture.- 1. Introduction.- 1.1. Significance of Studies with Diploid Human Cells.- 1.2. Implications for Carcinogenesis.- 2. Procedures.- 2.1. Cell Strains and Media.- 2.2. Assay for Cytotoxicity.- 2.3. Quantitating the Frequency of Drug-Resistant Colonies in the Population.- 2.4. Characterization of Drug-Resistant Colonies.- 3. Evidence that Excision Repair Can Eliminate Potentially Cytotoxic and Mutagenic Lesions from DNA.- 3.1. Potentially Cytotoxic Lesions.- 3.2. Potentially Mutagenic Lesions.- 4. Conclusion.- 5. References.- 12 Gene-Locus Mutation Assays in Diploid Human Lymphoblast Lines.- 1. Introduction.- 1.1. Sources and Care of Starter Cultures.- 1.2. Mutation Assays.- 2. Exposure.- 2.1. Duration.- 2.2. Limits to Statistical Precision.- 2.3. Treatment with Metabolic Activation.- 2.4. Posttreatment Handling.- 3. Determination of Colony-Forming Ability.- 4. Selection Systems.- 4.1. General Considerations.- 4.2. Potential Cell-Density Artifacts.- 4.3. Useful Selective Systems.- 5. Experimental Observations.- 5.1. Mutation at the hgprt Locus.- 5.2. Comparison of Mutation at the hgprt Locus in Different Human Lymphoblast Lines.- 5.3. Mutation at Other Loci.- 6. Discussion.- 6.1. Further Developments in Lymphoblast Mutation Assays.- 6.2. Further Uses of Lymphoblast Assays.- 7. References.- 13 The Need for Both in Vitro and in Vivo Systems in Mutagenicity Screening.- 1. Introduction.- 2. General Considerations of Mutagenicity Screening of Chemicals.- 2.1. Use of in Vitro and in Vivo Systems in Qualitative Testing.- 2.2. Use of in Vitro Systems Only in Qualitative Testing.- 2.3. Inadequacies of in Vitro Testing.- 2.4. Necessity for Combined Testing.- 3. Correlations between Carcinogenicity and Mutagenicity in Salmonella.- 3.1. Background.- 3.2. Statistical Considerations of Correlating.- 4. Construction of a Table of 465 Compounds with Known or Suspected Carcinogenic Activity (Table 4).- 4.1. International Agency for Research on Cancer (IARC).- 4.2. Environmental Protection Agency (EPA).- 4.3. Department of Health, Education and Welfare (DREW).- 4.4. Correlation Studies.- 5. Discussion of False Negatives from Table 4.- 5.1. Azo Compounds.- 5.2. Carbamyls and Thiocarbamyls.- 5.3. Phenyls.- 5.4. Benzodioxoles.- 5.5. Bactericides.- 5.6. Halogenated Compounds.- 5.7. Steroids.- 5.8. Antimetabolites.- 5.9. Hydrazines and N-Alkyl Compounds.- 5.10. Intercalating Agents.- 5.11. Chloroethylenes.- 5.12. Membrane-Specific Agents.- 5.13. Pyrazolinone.- 5.14. Mitotic Poisons.- 5.15. Cross-Linking Agents.- 5.16. Summary.- 6. Validation of Salmonella Testing as a Predictor of Carcinogenicity.- 7. Concluding Comments on Mutagenicity Testing.- 8. References.